KEGG   PATHWAY: mleu04915
Entry
mleu04915                   Pathway                                
Name
Estrogen signaling pathway - Mandrillus leucophaeus (drill)
Description
Estrogens are steroid hormones that regulate a plethora of physiological processes in mammals, including reproduction, cardiovascular protection, bone integrity, cellular homeostasis, and behavior. Estrogen mediates its cellular actions through two signaling pathways classified as "nuclear-initiated steroid signaling" and "membrane-initiated steroid signaling". In the "nuclear" pathway, estrogen binds either ERalpha or ERbeta, which in turn translocates to the nucleus, binds DNA at ERE elements and activates the expression of ERE-dependent genes. In "membrane" pathway, Estrogen can exert its actions through a subpopulation of ER at the plasma membrane (mER) or novel G-protein coupled E2 receptors (GPER). Upon activation of these receptors various signaling pathways (i.e. Ca2+, cAMP, protein kinase cascades) are rapidly activated and ultimately influence downstream transcription factors.
Class
Organismal Systems; Endocrine system
Pathway map
mleu04915  Estrogen signaling pathway
mleu04915

Other DBs
GO: 0030520
Organism
Mandrillus leucophaeus (drill) [GN:mleu]
Gene
105551527  ESR1; estrogen receptor isoform X1 [KO:K08550]
105538440  ESR2; estrogen receptor beta isoform X1 [KO:K08551]
105547864  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
105544357  HSP90AB1; heat shock protein HSP 90-beta isoform X1 [KO:K04079]
105536204  HSP90B1; endoplasmin [KO:K09487]
105529893  FKBP4; peptidyl-prolyl cis-trans isomerase FKBP4 [KO:K09571] [EC:5.2.1.8]
105544212  FKBP5; peptidyl-prolyl cis-trans isomerase FKBP5 [KO:K09571] [EC:5.2.1.8]
105554185  heat shock 70 kDa protein 1 isoform X1 [KO:K03283]
105554187  HSPA1L; heat shock 70 kDa protein 1-like [KO:K03283]
105528281  HSPA8; heat shock cognate 71 kDa protein isoform X1 [KO:K03283]
105554680  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
105535402  heat shock cognate 71 kDa protein-like isoform X1 [KO:K03283]
105551009  HSPA6; LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283]
105534028  NCOA1; nuclear receptor coactivator 1 [KO:K09101] [EC:2.3.1.48]
105537013  NCOA2; nuclear receptor coactivator 2 [KO:K11255]
105542274  NCOA3; LOW QUALITY PROTEIN: nuclear receptor coactivator 3 [KO:K11256] [EC:2.3.1.48]
105535165  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
105530711  EBAG9; receptor-binding cancer antigen expressed on SiSo cells isoform X1 [KO:K22455]
105531913  keratin, type I cytoskeletal 18-like [KO:K07604]
105552979  KRT20; keratin, type I cytoskeletal 20 [KO:K07604]
105552980  KRT23; keratin, type I cytoskeletal 23 isoform X1 [KO:K07604]
105552982  KRT39; keratin, type I cytoskeletal 39 [KO:K07604]
105552983  KRT40; keratin, type I cytoskeletal 40 [KO:K07604]
105553005  keratin, type I cuticular Ha3-I [KO:K07604]
105553006  KRT33B; keratin, type I cuticular Ha3-II [KO:K07604]
105553007  KRT34; keratin, type I cuticular Ha4 [KO:K07604]
105553008  KRT31; keratin, type I cuticular Ha1 isoform X1 [KO:K07604]
105553010  keratin, type I cuticular Ha7-like [KO:K07604]
105553012  KRT37; keratin, type I cuticular Ha7 [KO:K07604]
105553013  KRT38; keratin, type I cuticular Ha8 [KO:K07604]
105553014  KRT32; keratin, type I cuticular Ha2 [KO:K07604]
105553016  KRT35; keratin, type I cuticular Ha5 [KO:K07604]
105553017  KRT36; keratin, type I cuticular Ha6 [KO:K07604]
105553018  KRT13; keratin, type I cytoskeletal 13 isoform X1 [KO:K07604]
105553019  KRT15; keratin, type I cytoskeletal 15 [KO:K07604]
105553020  KRT19; keratin, type I cytoskeletal 19 [KO:K07604]
105553021  KRT9; keratin, type I cytoskeletal 9 [KO:K07604]
105553022  keratin, type I cytoskeletal 16 isoform X1 [KO:K07604]
105553024  keratin, type I cytoskeletal 17 [KO:K07604]
105553025  KRT10; keratin, type I cytoskeletal 10 isoform X1 [KO:K07604]
105553026  KRT28; keratin, type I cytoskeletal 28 [KO:K07604]
105553027  KRT27; keratin, type I cytoskeletal 27 isoform X1 [KO:K07604]
105553028  KRT25; keratin, type I cytoskeletal 25 [KO:K07604]
105553029  keratin, type I cytoskeletal 24 [KO:K07604]
105553087  KRT12; keratin, type I cytoskeletal 12 [KO:K07604]
105553090  KRT26; keratin, type I cytoskeletal 26 [KO:K07604]
105528280  KRT18; keratin, type I cytoskeletal 18 [KO:K07604]
105537251  keratin, type I cytoskeletal 18-like [KO:K07604]
105550866  keratin, type I cytoskeletal 18 [KO:K07604]
105545336  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
105528546  GREB1; protein GREB1 [KO:K27477]
105555565  TFF1; trefoil factor 1 [KO:K22456]
105542725  PGR; progesterone receptor isoform X1 [KO:K08556]
105529939  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
105553040  RARA; retinoic acid receptor alpha isoform X1 [KO:K08527]
105540805  FOS; proto-oncogene c-Fos isoform X1 [KO:K04379]
105534921  JUN; transcription factor AP-1 [KO:K04448]
105554908  SP1; transcription factor Sp1 [KO:K04684]
105537862  G-protein coupled estrogen receptor 1 [KO:K04246]
105537874  G-protein coupled estrogen receptor 1-like [KO:K04246]
105548339  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
105548340  neuroendocrine secretory protein 55 [KO:K04632]
105535793  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
105533444  MMP2; 72 kDa type IV collagenase isoform X1 [KO:K01398] [EC:3.4.24.24]
105542292  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
105528340  HBEGF; proheparin-binding EGF-like growth factor [KO:K08523]
105541972  uncharacterized protein LOC105541972 [KO:K08041] [EC:4.6.1.1]
105535662  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
105534027  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
105532738  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
105533183  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105544918  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
105545643  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
105530895  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
105541508  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
105532068  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
105540992  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
105538055  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105549382  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105548041  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
105538852  ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374]
105539715  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
105554054  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
105554841  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
105530028  CREB3L3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
105550535  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105533710  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
105531497  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
105529594  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
105544828  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
105548833  SHC2; SHC-transforming protein 2 [KO:K17447]
105535962  SHC3; SHC-transforming protein 3 [KO:K17448]
105529990  SHC4; SHC-transforming protein 4 [KO:K17449]
105538707  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
105551898  SOS1; son of sevenless homolog 1 [KO:K03099]
105553627  SOS2; son of sevenless homolog 2 [KO:K03099]
105549333  HRAS; GTPase HRas isoform X1 [KO:K02833]
105550009  KRAS; GTPase KRas [KO:K07827]
105554356  NRAS; GTPase NRas isoform X1 [KO:K07828]
105542175  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105530797  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105530027  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105541405  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
105544764  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105539923  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105552763  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
105549588  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
105547376  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105543389  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105531763  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
105540494  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105541755  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105542359  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105548308  GABBR1; gamma-aminobutyric acid type B receptor subunit 1 isoform X1 [KO:K04615]
105549294  GABBR2; gamma-aminobutyric acid type B receptor subunit 2 [KO:K04615]
105548989  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
105543912  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
105530947  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
105533439  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
105548107  KCNJ3; G protein-activated inward rectifier potassium channel 1 isoform X1 [KO:K04997]
105542557  G protein-activated inward rectifier potassium channel 2 [KO:K05000]
105532278  KCNJ9; G protein-activated inward rectifier potassium channel 3 [KO:K05002]
105528620  KCNJ5; G protein-activated inward rectifier potassium channel 4 isoform X1 [KO:K04999]
105534022  POMC; pro-opiomelanocortin [KO:K05228]
105532578  OPRM1; mu-type opioid receptor isoform X1 [KO:K04215]
105543983  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
105542500  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
105546224  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105552818  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
105553023  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
105549095  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
105528641  ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
105555461  ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959]
105544182  ITPR3; inositol 1,4,5-trisphosphate receptor type 3 isoform X1 [KO:K04960]
105531569  CALM3; calmodulin isoform X1 [KO:K02183]
105535291  CALM1; calmodulin isoform X1 [KO:K02183]
105528838  CALM2; calmodulin isoform X1 [KO:K02183]
105535727  CALML3; calmodulin-like protein 3 [KO:K02183]
105535728  CALML5; calmodulin-like protein 5 [KO:K02183]
105544662  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
105530955  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
105542707  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
105535378  GRM1; metabotropic glutamate receptor 1 [KO:K04603]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00238  Potassium cation
C00334  4-Aminobutanoate
C00533  Nitric oxide
C00575  3',5'-Cyclic AMP
C00951  Estradiol-17beta
C01245  D-myo-Inositol 1,4,5-trisphosphate
Reference
PMID:16516516
  Authors
Zhang D, Trudeau VL
  Title
Integration of membrane and nuclear estrogen receptor signaling.
  Journal
Comp Biochem Physiol A Mol Integr Physiol 144:306-15 (2006)
DOI:10.1016/j.cbpa.2006.01.025
Reference
PMID:19187465
  Authors
Roepke TA, Qiu J, Bosch MA, Ronnekleiv OK, Kelly MJ
  Title
Cross-talk between membrane-initiated and nuclear-initiated oestrogen signalling in the hypothalamus.
  Journal
J Neuroendocrinol 21:263-70 (2009)
DOI:10.1111/j.1365-2826.2009.01846.x
Reference
PMID:19700741
  Authors
McCarthy MM
  Title
The two faces of estradiol: effects on the developing brain.
  Journal
Neuroscientist 15:599-610 (2009)
DOI:10.1177/1073858409340924
Reference
PMID:18538919
  Authors
Kelly MJ, Ronnekleiv OK
  Title
Membrane-initiated estrogen signaling in hypothalamic neurons.
  Journal
Mol Cell Endocrinol 290:14-23 (2008)
DOI:10.1016/j.mce.2008.04.014
Reference
PMID:16112267
  Authors
Kelly MJ, Qiu J, Ronnekleiv OK
  Title
Estrogen signaling in the hypothalamus.
  Journal
Vitam Horm 71:123-45 (2005)
DOI:10.1016/S0083-6729(05)71005-0
Reference
PMID:18253054
  Authors
Raz L, Khan MM, Mahesh VB, Vadlamudi RK, Brann DW
  Title
Rapid estrogen signaling in the brain.
  Journal
Neurosignals 16:140-53 (2008)
DOI:10.1159/000111559
Reference
PMID:15862823
  Authors
Malyala A, Kelly MJ, Ronnekleiv OK
  Title
Estrogen modulation of hypothalamic neurons: activation of multiple signaling pathways and gene expression changes.
  Journal
Steroids 70:397-406 (2005)
DOI:10.1016/j.steroids.2005.03.004
Reference
PMID:14573532
  Authors
Qiu J, Bosch MA, Tobias SC, Grandy DK, Scanlan TS, Ronnekleiv OK, Kelly MJ
  Title
Rapid signaling of estrogen in hypothalamic neurons involves a novel G-protein-coupled estrogen receptor that activates protein kinase C.
  Journal
J Neurosci 23:9529-40 (2003)
DOI:10.1523/JNEUROSCI.23-29-09529.2003
Reference
PMID:14993035
  Authors
Kelly MJ, Qiu J, Ronnekleiv OK
  Title
Estrogen modulation of G-protein-coupled receptor activation of potassium channels in the central nervous system.
  Journal
Ann N Y Acad Sci 1007:6-16 (2003)
DOI:10.1196/annals.1286.001
Reference
PMID:19549587
  Authors
Meyer MR, Haas E, Prossnitz ER, Barton M
  Title
Non-genomic regulation of vascular cell function and growth by estrogen.
  Journal
Mol Cell Endocrinol 308:9-16 (2009)
DOI:10.1016/j.mce.2009.03.009
Reference
PMID:20694192
  Authors
do Nascimento GR, Barros YV, Wells AK, Khalil RA
  Title
Research into Specific Modulators of Vascular Sex Hormone Receptors in the Management of Postmenopausal Cardiovascular Disease.
  Journal
Curr Hypertens Rev 5:283-306 (2009)
DOI:10.2174/157340209789587717
Reference
PMID:15695368
  Authors
Bjornstrom L, Sjoberg M
  Title
Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes.
  Journal
Mol Endocrinol 19:833-42 (2005)
DOI:10.1210/me.2004-0486
Reference
PMID:16270355
  Authors
Manavathi B, Kumar R
  Title
Steering estrogen signals from the plasma membrane to the nucleus: two sides of the coin.
  Journal
J Cell Physiol 207:594-604 (2006)
DOI:10.1002/jcp.20551
Reference
PMID:21844907
  Authors
Prossnitz ER, Barton M
  Title
The G-protein-coupled estrogen receptor GPER in health and disease.
  Journal
Nat Rev Endocrinol 7:715-26 (2011)
DOI:10.1038/nrendo.2011.122
Reference
PMID:21742056
  Authors
Meyer MR, Prossnitz ER, Barton M
  Title
The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function.
  Journal
Vascul Pharmacol 55:17-25 (2011)
DOI:10.1016/j.vph.2011.06.003
Reference
PMID:19767412
  Authors
Maggiolini M, Picard D
  Title
The unfolding stories of GPR30, a new membrane-bound estrogen receptor.
  Journal
J Endocrinol 204:105-14 (2010)
DOI:10.1677/JOE-09-0242
Reference
PMID:19464786
  Authors
Prossnitz ER, Maggiolini M
  Title
Mechanisms of estrogen signaling and gene expression via GPR30.
  Journal
Mol Cell Endocrinol 308:32-8 (2009)
DOI:10.1016/j.mce.2009.03.026
Reference
PMID:12650715
  Authors
Kelly MJ, Qiu J, Wagner EJ, Ronnekleiv OK
  Title
Rapid effects of estrogen on G protein-coupled receptor activation of potassium channels in the central nervous system (CNS).
  Journal
J Steroid Biochem Mol Biol 83:187-93 (2002)
DOI:10.1016/S0960-0760(02)00249-2
Reference
PMID:9278514
  Authors
Paech K, Webb P, Kuiper GG, Nilsson S, Gustafsson J, Kushner PJ, Scanlan TS
  Title
Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites.
  Journal
Science 277:1508-10 (1997)
DOI:10.1126/science.277.5331.1508
Reference
PMID:12421825
  Authors
Razandi M, Pedram A, Park ST, Levin ER
  Title
Proximal events in signaling by plasma membrane estrogen receptors.
  Journal
J Biol Chem 278:2701-12 (2003)
DOI:10.1074/jbc.M205692200
Reference
PMID:18755790
  Authors
Roepke TA, Xue C, Bosch MA, Scanlan TS, Kelly MJ, Ronnekleiv OK
  Title
Genes associated with membrane-initiated signaling of estrogen and energy homeostasis.
  Journal
Endocrinology 149:6113-24 (2008)
DOI:10.1210/en.2008-0769
Reference
PMID:21779010
  Authors
Thomas C, Gustafsson JA
  Title
The different roles of ER subtypes in cancer biology and therapy.
  Journal
Nat Rev Cancer 11:597-608 (2011)
DOI:10.1038/nrc3093
Related
pathway
mleu04010  MAPK signaling pathway
mleu04020  Calcium signaling pathway
mleu04151  PI3K-Akt signaling pathway
mleu04270  Vascular smooth muscle contraction
mleu04727  GABAergic synapse
mleu04913  Ovarian steroidogenesis
KO pathway
ko04915   
LinkDB

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